Osteoporosis is a major public health problem in developed countries. By the year 2050, it is estimated that the incidence of this debilitating disorder will significantly increase both in terms of the numbers of women and men affected and in the escalating cost of patient care. Recent studies indicate that there is a strong genetic component in the development of osteoporosis. The studies also indicate that osteoporosis is a complex disorder with several genes interacting to set the stage for bone loss with advancing age and in certain younger individuals. The Old Order Amish of Lancaster County, Pennsylvania, are a homogeneous population that is ideal for the identification of osteoporosis susceptibility genes by candidate gene analysis and positional cloning methodology. Osteoporotic probands have been identified by history of vertebral or hip fracture and by bone mineral density (BMD) measurements. In addition, the serum markers procollagen type I carboxyl terminal peptide (PICP), osteocalcin, 25 hydroxy vitamin D, and the urinary marker deoxypyridinoline (DPD), have been analyzed. During the current reporting period, the data including BMD measurements and serum and urinary bone metabolism markers have been statistically analyzed for possible correlations for 135 participants. The defined osteoporotic population exhibited differences compared to normal cohorts in terms of BMD, DPD and PICP values. The serum markers (osteocalcin and 25 hydroxy vitamin D) showed no mean differences between osteoporotic and normal participants. Between the two groups, there were no significant age or gender differences. Within the osteoporotic group, however, age and gender differences were apparent with men and women exhibiting differing rates of bone loss (as measured by BMD and DPD), and differing ages of diagnosis. With the two study populations phenotypically defined, the stage is now set for an initial screening of candidate gene polymorphisms. The polymorphisms to be studied include those of the vitamin D receptor, estrogen receptor alpha and beta, as well as, type I collagen. CORE LABORATORY ONLY; NO INPATIENT DAYS OR OUTPATIENT VISITS.